The influence of sodium balance and furosemide administration on acute amphotericin B-induced nephrotoxicity has been investigated in the anesthetized dog. In sodium-depleted dogs, amphotericin B (1 mg/kg i.v.) reduced renal blood flow by 32% and glomerular filtration rate by 90% 40 min after the infusion and 32 and 65%, respectively, 140 min after infusion. Although filtration fraction was reduced, fractional sodium excretion increased 13-fold. Renal renin secretion rate decreased by 64%. Prior sodium loading abolished the acute response to amphotericin B. Pretreatment of sodium-depleted dogs with furosemide (5 mg/kg bolus followed by 260 micrograms/kg/min i.v.) attenuated the reduction in renal blood flow and glomerular filtration rate produced by amphotericin B. The data indicate that acute reductions in renal blood flow and glomerular filtration rate in response to amphotericin B infusion are not direct but related to sodium status. The changes do not seem to be mediated by the renin-angiotensin system and can be inhibited by sodium loading and attenuated by concurrent furosemide administration. These observations are consistent with the hypothesis that the acute response is mediated by tubulo-glomerular feedback.